Blocking a protein known as CDK7 could prevent heart damage associated with a commonly used cancer chemotherapy medication, according to a study led by scientists at Washington State University. Importantly, the researchers also found that inhibiting CDK7 could help enhance the medication’s cancer-killing capability.
Based on an animal model, the study findings could provide a foundation for future treatment strategies to reduce chemotherapy-related heart toxicity and increase treatment effectiveness. This could ultimately help increase the lifespan of people with cancer. Heart damage related to chemotherapy treatment can surface decades after treatment and can result in heart attacks, heart failure, cardiomyopathy and other types of heart disease.
Published in the journal Cardiovascular Research, the WSU study focused on doxorubicin, a chemotherapy drug used to treat breast cancer, lymphoma, leukemia and other cancers. Capable of killing a wide range of cancer cells, doxorubicin and other similar chemotherapy medications are known to be toxic to the heart. Despite this toxicity, the drug still sees a lot of use.
“Doxorubicin remains the mainstay treatment for certain cancer types for which targeted therapies or other better treatments are not available,” said senior study author Zhaokang Cheng, an associate professor in the WSU College of Pharmacy and Pharmaceutical Sciences.
Cheng has been working to unravel the underlying mechanisms of doxorubicin-induced heart toxicity to make the use of doxorubicin safer for patients who rely on the drug. This new study builds on findings from earlier research that showed that doxorubicin activates a protein known as CDK2. That protein then activates another known as FOXO1, which causes heart cells to die. Cheng’s team collaborated with WSU cancer biology researcher Boyang (Jason) Wu to take a closer look at CDK7, a protein that helps fuel cell growth and has been shown to play a role in the development of cancer.
The researchers found that CDK7 activated CDK2, which set off the chain of molecular signals that eventually led to heart cell death. They also showed that mice that lacked the CDK7 gene were protected from doxorubicin-induced heart toxicity. Next, they used a CDK7 inhibitor drug known as THZ1 to block the protein’s activity and examine the impact on heart health and cancer growth. A similar inhibitor is currently being tested as an anticancer drug in clinical trials, but its effect on the heart is still not clear.
“We are the first to study the effect of THZ1 on the heart and on tumor growth in the same model,” said study first author Jingrui Chen, a WSU research associate. “And what we found is that this CDK7 inhibitor drug can increase heart function and at the same time inhibit tumor growth.”
Though more research is needed, the researchers said their findings suggest that combining doxorubicin and THZ1 could help prevent heart damage and increase the effectiveness of chemotherapy treatment.
The researchers’ next step is to test the effect of THZ1 on heart damage and cancer growth in younger mice and follow them longer. This would more closely mimic long-term doxorubicin-induced heart toxicity seen in childhood cancer survivors. They also plan to look at other proteins that may somehow be involved in the signaling pathway that underlies doxorubicin-related heart damage.
Primary funding support for the study came from the National Heart, Lung and Blood Institute — a component of the National Institutes of Health — with additional support from the National Cancer Institute.

Telemedicine visits for cancer care may not only be more convenient and easier to schedule than in-person appointments, they’re also better for the planet, new research by Dana-Farber Cancer Institute scientists shows.
Based on an analysis of data from a regional cancer center, the researchers calculate that, nationwide, cancer care that utilizes telehealth and local care would generate 33.1% less greenhouse gas emissions than the traditional model of in-person care, primarily because of reduced travel to medical appointments. The findings presented at the annual meeting of the American Society of Clinical Oncology (ASCO) and published simultaneously in the journal JAMA Oncology, suggest that an approach to care adopted during the COVID-19 pandemic can have significant environmental benefits.
“While health care in the United States provides health benefits to many people, it generates substantial amounts of greenhouse gas emissions that drive climate change and inadvertently harm health,” says Andrew Hantel, MD, a faculty member in the Divisions of Leukemia and Population Sciences at Dana-Farber who led the study with Gregory Abel, MD, MPH, a senior physician at Dana-Farber, and Jonathan Slutzman, MD, of Massachusetts General Hospital. “We wanted to explore the potential reductions in emissions that can be achieved with a decentralized approach to cancer care that includes telehealth. To do so, we used data generated during the ‘natural experiment’ of the pandemic, when care shifted from an in-person to a telemedicine-preferred model.”
The researchers calculated the amount of carbon dioxide emitted per visit-day at Dana-Farber during two time periods: March-December 2020, when the pandemic prompted the Institute to shift largely to telemedicine; and March 2015-February 2020, when a traditional in-person model was in place. (A visit-day is the combined visits a person has at a healthcare facility in a single day.)
They began by listing all the components of a clinical visit, both in-person and telehealth. For in-person visits, that includes everything that happens from the time a patient leaves home for an appointment until the time they return — such as driving to the hospital, parking the car, taking the elevator to the clinic, using hand sanitizer, using the bathroom, and driving back home. They also factored in the use of electricity for lights and computers, even the paper that covers the exam room table. Using a variety of databases, they then determined the carbon dioxide emissions associated with each of these. (For products like hand sanitizers, there is data on the number of emissions used in making and disposing of each of their constituent parts.)
For telehealth visits, there were far fewer aspects to track — mainly, computer and internet usage by the patient and clinician.
They found that per visit-day emissions of carbon dioxide at Dana-Farber were 36.4 kilograms lower during the telemedicine period than the in-person period, an 81.3% decline. They then calculated what emissions levels during the pre-pandemic period would have been if telemedicine had been in place and extrapolated it to the whole U.S. population. They found that CO2 emissions would have been reduced by 75.3 million kilograms, a 33.1% drop. (The more modest decline on a national level than at Dana-Farber reflects differences between the national population and those treated at Dana-Farber, such as the higher proportion of patients with rare cancers, Hantel explains. Patients with more uncommon cancers often travel further to receive care, resulting in higher emissions levels.) At the national scale, the 75.3-million-kilogram decline in CO2 corresponds to a modest reduction in human health harms (15.0-47.7 disability adjusted life-years).
“Telemedicine, and decentralized oncology care in general, involve a complex balance of risks and benefits that vary across the population,” Hantel observes. “On the plus side, they can increase the reach of expert care while reducing travel, time, and cost for patients. But they also have the potential to add rather than replace visits, which may be difficult for older adults and those without good internet connections, and in some cases may reduce clinicians’ ability to appropriately diagnose and treat. Our findings add another layer to this conversation, showing that emissions reduction is an additional benefit of this approach to care.”

A new study from the University of Michigan Health Rogel Cancer Center reveals a connection between the most common type of white blood cells, which act as a first defense in the body’s immune system, and a severe complication of CAR T-Cell immunotherapy.
The findings, out now in Blood Advances, show that a process called NETosis, in which neutrophils eject their DNA to create webs, may contribute to the development of cytokine release syndrome (CRS), a potentially life-threatening hyper-activation of the immune system.
Further, the team, led by Muneesh Tewari, M.D., Ph.D., Ray and Ruth Anderson-Laurence Sprague Memorial Research Professor in the Department of Internal Medicine, and Sung Won Choi, M.D., M.S., Edith S. Briskin and Shirley K. Schlafer Foundation Research Professor of Pediatrics, identified certain proteins that are biomarkers of NETosis and could predict which patients are likely to develop CRS before they develop symptoms.
Tewari explains that there are FDA-approved drugs that can be used to affect neutrophils, like disulfiram used to treat alcohol abuse. Though typically prescribed for other conditions, these drugs could be leveraged to inhibit NETosis and prevent CRS.
“We identified biomarkers that are part of the ‘nets’ the neutrophils cast, and an indication that CRS is likely to occur,” Tewari said. “In addition to this strong correlation, we hypothesize that NETosis is also contributing to the development of CRS. We want to test this idea in preclinical models, and eventually in clinical trials, to see if we can inhibit the net formation and reduce the risk of CRS in patients.”
Over 70% of patients develop cytokine release syndrome; about 15%-20% of those cases are severe and could require admission to an intensive care unit because of low blood pressure, increased heart rate, shortness of breath, or major organs shutting down.
Patients can develop cytokine release syndrome within a week after receiving CAR T-cell infusions. Tewari explains that little is known about the mechanisms happening during that first week, before CRS symptoms are present. Given this lack of knowledge, the research team used proteomics analysis to measure hundreds of proteins in blood samples from patients who underwent CAR T-cell therapy, both those who went on to develop CRS and those who didn’t.

“We found dozens of proteins that seem to be different in patients who go on to develop CRS versus those who don’t. We also found less than 10 proteins that seemed to be different before patients developed CRS, even before they got the treatment,” Tewari explained.
The team also analyzed what proteins in the blood plasma change over time as CRS developed. “We noticed that neutrophil-related proteins were coming up. That tipped us off to think more about neutrophils specifically, which let us to NETosis,” Tewari said.
The process of NETosis is like its name suggests. When neutrophils are triggered, which normally might happen at the onset of a bacterial infection, for example, they eject their DNA, which is packed tightly inside the nucleus, into structures resembling “nets” that can capture and contain the bacteria.
In patients that go on to develop CRS, Tewari explains that while there is “no bacteria, per se,” the neutrophils are confused and act as though there’s an invader. “We don’t yet know why, but in some patients, their neutrophils are already triggered and on high alert. They’re already forming these nets, which activates the entire immune system and makes their bodies more prone to over-react by making a flood of cytokines, producing CRS.”
In addition to pursuing clinical trials to see if certain FDA-approved drugs can help suppress NETosis, Tewari says this study could help reveal how stress affects the body on a cellular level. “We’re seeing more and more how a triggered immune system makes a difference in terms of outcomes, especially with cytokine release syndrome,” Tewari said.
“There’s early data to suggest that psychological stress can affect neutrophil function. This study is another piece of the puzzle that could lead to more insights into how stress can negatively impact the body and contribute to illness.”

For survivors of strokes, which afflict nearly 800,000 Americans each year, regaining fine motor skills like writing and using utensils is critical for recovering independence and quality of life. But getting intensive, frequent rehabilitation therapy can be challenging and expensive.
Now, researchers at NYU Tandon School of Engineering are developing a new technology that could allow stroke patients to undergo rehabilitation exercises at home by tracking their wrist movements through a simple setup: a smartphone strapped to the forearm and a low-cost gaming controller called the Novint Falcon.
The Novint Falcon, a desktop robot typically used for video games, can guide users through specific arm motions and track the trajectory of its controller. But it cannot directly measure the angle of the user’s wrist, which is essential data for therapists providing remote rehabilitation.
In a paper presented at SPIE Smart Structures + Nondestructive Evaluation 2024, the researchers proposed using the Falcon in tandem with a smartphone’s built-in motion sensors to precisely monitor wrist angles during rehab exercises.
“Patients would strap their phone to their forearm and manipulate this robot,” said Maurizio Porfiri, NYU Tandon Institute Professor and director of its Center for Urban Science + Progress (CUSP), who is the paper’s senior author. “Data from the phone’s inertial sensors can then be combined with the robot’s measurements through machine learning to infer the patient’s wrist angle.”
The researchers collected data from a healthy subject performing tasks with the Falcon while wearing motion sensors on the forearm and hand to capture the true wrist angle. They then trained an algorithm to predict the wrist angles based on the sensor data and Falcon controller movements.
The resulting algorithm could predict wrist angles with over 90% accuracy, a promising initial step toward enabling remote therapy with real-time feedback in the absence of an in-person therapist.

“This technology could allow patients to undergo rehabilitation exercises at home while providing detailed data to therapists remotely assessing their progress,” Roni Barak Ventura, the paper’s lead author who was an NYU Tandon postdoctoral fellow at the time of the study. “It’s a low-cost, user-friendly approach to increasing access to crucial post-stroke care.”
The researchers plan to further refine the algorithm using data from more subjects. Ultimately, they hope the system could help stroke survivors stick to intensive rehab regimens from the comfort of their homes.
“The ability to do rehabilitation exercises at home with automatic tracking could dramatically improve quality of life for stroke patients,” said Barak Ventura. “This portable, affordable technology has great potential for making a difficult recovery process much more accessible.”
This study adds to NYU Tandon’s body of work that aims to improve stroke recovery. In 2022, Researchers from NYU Tandon began collaborating with the FDA to design a regulatory science tool based on biomarkers to objectively assess the efficacy of rehabilitation devices for post-stroke motor recovery and guide their optimal usage. A study from earlier this year unveiled advances in technology that uses implanted brain electrodes to recreate the speaking voice of someone who has lost speech ability, which can be an outcome from stroke.

The sharks we know today as the open ocean’s top predators evolved from stubby bottom dwellers during a dramatic episode of global warming millions of years ago.
A massive outpouring of volcanic lava about 93 million years ago sent carbon dioxide levels soaring, creating a greenhouse climate that pushed ocean temperatures to their hottest. UC Riverside researchers discovered that some sharks responded to the heat with elongated pectoral fins.
This discovery is documented in a paper published today in the journal Current Biology. It was made by taking body length and fin measurements from over 500 living and fossilized shark species.
“The pectoral fins are a critical structure, comparable to our arms,” said UCR biology doctoral student and paper first author Phillip Sternes. “What we saw upon review of a massive data set, was that these fins changed shape as sharks expanded their habitat from the bottom to the open ocean.”
Longer pectoral fins help make shark movements much more efficient. “Their fins are comparable to the wings of commercial airplanes, long and narrow, to minimize the amount of energy needed for movement,” Sternes said.
The researchers also saw that the open-water sharks got faster compared to bottom dwelling sharks. “Shark muscle is very sensitive to temperature,” said Tim Higham, professor in UCR’s Department of Evolution, Ecology, and Organismal Biology and paper co-author.
“The data helped us make a correlation between higher temperatures, tail movement, and swimming speeds,” Higham said.

Most living shark species are still bottom dwellers, occupying what scientists refer to as the benthic zone. These benthic sharks do not loom as large in popular culture as their fierce open-water relatives. Many of the bottom dwellers are slender, flatter, more medium-sized predators.
Only about 13% of modern sharks are fast-swimming open-water predators. The researchers believe that breathing may have become difficult for their ancient relatives. Oxygen levels near the bottom during the Cretaceous period likely dropped as the heat increased.
Modern sea surface temperatures average about 68 degrees Fahrenheit. In the Cretaceous they were much warmer, reaching an average of about 83 degrees. The high heat of the Cretaceous did not happen overnight, and neither did the sharks’ evolution.
“We had pretty warm open-sea surface temperatures throughout the era, and then a distinct spike that took place over a one- or two-million-year period,” said associate professor at Claremont McKenna College and paper co-author Lars Schmitz.
As global warming drove an evolution in some groups of animals, including sharks, it caused the extinction of others. Because those evolutionary changes happened on a longer time scale in the past, it is difficult to predict exactly how sharks or other marine life will respond to current warming trends.
Biologists are seeing some sharks, including tropical species like tiger and bull sharks, starting to swim farther north. But it is unclear whether threatened sharks will again be able to adapt where they live and survive the rapidly increasing heat.
“The temperature is going up so fast now, there is nothing in the geologic record I am aware of that we can use for a true comparison,” Sternes said.

Researchers at the RIKEN Center for Integrative Medical Sciences (IMS) have discovered numerous age-related changes in the lipid metabolism of mice, across both organs and sexes. Among these changes was the selective accumulation, throughout the body, of certain lipids produced by gut bacteria as the mice aged. They also discovered a sex difference in the kidneys and a gene responsible for it. Published in Nature Aging, this study could lead to better understanding of chronic age-related conditions like Alzheimer’s disease, atherosclerosis, kidney disease, and cancer.
Lipids, often in the form of fats or oils, are essential molecules for storing energy in our bodies, among other things. In addition, lipids act as signaling molecules and as components of cell membranes. Metabolism — the breakdown of biomolecules such as lipids and sugars into their component parts — slows down as we age, which helps explain why it’s easier to gain weight, and more difficult to lose it, as we get older. Although this has been known for over 50 years, how changes in lipid metabolism in particular affects lifespan and health remain unclear. In their recent study, Hiroshi Tsugawa and his team at RIKEN IMS reasoned that before this question can be fully answered, we need to know what the actual changes are, in great detail. Only then can scientists begin looking for links between aging lipid metabolism and human health. Toward this end, they used mice to develop an atlas of age-related changes in lipid metabolites.
By using a cutting-edge technique to take multiple snapshots of the mouse lipidome — all lipid metabolites present in a biological sample — the researchers found that BMP type lipids increased with age in the kidneys, liver, lungs, muscles, spleen, and small intestine of the mice. These lipids play key roles in cholesterol transport and the breakdown of biomolecules within cellular recycling centers called lysosomes. Age-related lysosomal damage might result in cells making more BMPs, which could lead to further metabolic changes, such as increasing cholesterol derivatives in the kidney.
The researchers also investigated the impact of gut bacteria on the lipidome, discovering that while gut bacteria produced many structurally unique lipids, only sulfonolipids increased with age in the liver, kidney, and spleen. In fact, no other group of lipid metabolites from gut bacteria were even detected in these peripheral tissues. “As this kind of lipid is known to be involved in regulating immune responses, the next phase of our research will involve testing the gut bacteria-derived sulfonolipids to determine their structure and physiological functions,” says Tsugawa.
The researchers also found age-related sex differences in the mouse lipidome, particularly in the kidneys, with levels of the lipid metabolite galactosylceramide being higher in older male mice than in older females. This discrepancy was attributed to increased expression of the UGT8 gene in male mice. Understanding sex-specific metabolic differences like this could shed light on susceptibility to age-related diseases humans.
“Our research has comprehensively characterized the changes in the lipidome that occur in the mouse with aging. In doing so, we have created at atlas that will serve as an important global resource,” says Tsugawa. “Next, we must extend this type of study to the human lipidome and microbiome.” The findings highlight the importance of understanding how lipid metabolism changes as we age, and the potential of targeting the lipidome when designing treatments for age-related diseases.

Healthy adults under the age of 75 are unlikely to benefit from taking more than the daily intake of vitamin D recommended by the Institutes of Medicine (IOM) and do not require testing for vitamin D levels, according to a new Clinical Practice Guideline issued today by the Endocrine Society. For children, pregnant people, adults older than 75 years and adults with high-risk prediabetes, the guideline recommends vitamin D higher than the IOM recommended daily allowance.
Vitamin D use and blood vitamin D levels have been associated with many common diseases. However, whether vitamin D supplementation lowers the risk of these diseases and what vitamin D blood levels are needed for better health have been debated for years.
In this new guideline, the panel of experts established guidelines for vitamin D use and testing for vitamin D levels in healthy persons without established indications for vitamin D treatment or testing. The guideline relied on clinical trials to develop the recommendations.
The guideline, titled “Vitamin D for the Prevention of Disease: An Endocrine Society Clinical Practice Guideline,” was published online and will appear in the August 2024 print issue of The Journal of Clinical Endocrinology & Metabolism (JCEM), a publication of the Endocrine Society.
“The goal of this guideline was to address the vitamin D requirements for disease prevention in a generally healthy population with no underlying conditions that would put them at risk of impaired vitamin D absorption or action,” said Marie Demay, M.D., of Harvard Medical School and Massachusetts General Hospital in Boston, Mass. Demay is the chair of the panel that developed the guideline. “Healthy populations who may benefit from higher dose vitamin D supplements are those 75 and older, pregnant people, adults with prediabetes, and children and adolescents 18 and younger, but we do not recommend routine testing for vitamin D levels in any of these groups.”
Key recommendations from the guideline include: We suggest against vitamin D supplements at doses beyond the reference dietary intakes recommended by the IOM in healthy adults under 75 years old. We identified the following populations that may benefit from supplementation above the intakes recommended by the IOM because of the potential to reduce specific health risks: Children and adolescents 18 and younger — potential to prevent nutritional rickets and to reduce the chance of respiratory infections. Individuals 75 and older — potential to lower mortality risk. Pregnant people — potential to reduce risk of pre-eclampsia, intra-uterine mortality, preterm birth, small-for-gestational age birth and neonatal mortality. People with prediabetes — potential to reduce progression to diabetes. In adults ages 50 years and older who have indications for vitamin D supplementation or treatment, we suggest daily, lower-dose vitamin D instead of non-daily, higher-dose vitamin D. We suggest against routine testing for 25-hydroxyvitamin D levels in any of the populations studied, since outcome-specific benefits based on these levels have not been identified. This includes 25-hydroxyvitamin D screening in people with dark complexion or obesity.Even though the evidence on the role of vitamin D in health and disease has increased over the last decade, the panel noted many limitations in the available evidence. For example, many of the large clinical trials were not designed for several of the outcomes that they reported, and the studied populations had vitamin D blood levels that most would consider adequate to begin with. Based on insufficient evidence, the panel could not determine specific blood-level thresholds for 25-hydroxyvitamin D for adequacy or for target levels for disease prevention.
Other members of the Endocrine Society writing committee that developed this guideline include: Anastassios Pittas (co-chair) of Tufts Medical Center in Boston, Mass.; Daniel Bikle of the University of California San Francisco in San Francisco, Calif.; Dima Diab of the University of Cincinnati in Cincinnati, Ohio; Mairead Kiely of University College Cork in Cork, Ireland; Marise Lazaretti-Castro of Universidade Federal de Sao Paulo in Sao Paulo, Brazil; Paul Lips of Amsterdam University Medical Center in Amsterdam, Netherlands; Deborah Mitchell of Massachusetts General Hospital and Harvard Medical School in Boston, Mass.; M. Hassan Murad of the Mayo Clinic in Rochester, Minn.; Shelley Powers of American Bone Health in Raleigh, N.C.; Sudhaker Rao of Henry Ford Health in Detroit, Mich. and Michigan State University in Lansing, Mich.; Robert Scragg of The University of Auckland in Auckland, New Zealand; John Tayek of Harbor-University of California Los Angeles Medical Center in Torrance, Calif.; Amy Valent of Oregon Health & Science University in Portland, Ore.; Judith Walsh of the University of California San Francisco in San Francisco, Calif.; and Christopher McCartney of West Virginia University in Morgantown, W.Va.

7 hours agoGetty ImagesCaring for patients in hospital corridors has become “normal”, despite being unsafe and unacceptable for patients, says a report from the Royal College of Nursing.

An “ultra-sensitive” new blood test can predict if breast cancer will return years before the disease shows up on scans, researchers say.

The Conservatives have promised to build 100 new GP surgeries in England and boost the number of available appointments by allowing more treatments in the community if they win the election.